Previous studies by the principal investigator have shown that hamster serum fraction enriched for alpha 2 macroglobulin (alpha 2 M) differentially inhibits stimulation of lymphocytes by B cell mitogens. These same serum fractions possessed protease-inhibitor activity. The purpose of this study is to extend biochemical purification of alpha 2 M and further analyze its biological role. Initial experiments will be directed toward biochemical isolation and characterization of alpha 2 M from hamster serum. A monospecific antiserum will be generated in rabbits. The following biological characteristics of alphas 2 M from serum will be investigated: (1) The role of alpha 2 M in proliferation will be analyzed by adding alpha 2 M serum fractions to short-term primary antibody-forming cell cultures. (2) Cells bearing surface alpha 2 M will be localized and distribution patterns followed utilizing immuno-fluorescent antibody techniques. Radiolabeled alpha 2 M may identify subpopulations of cells which bind alpha 2 M. (3) Various cell populations will be cultured in the presence of radiolabeled amino acid to permit identification of cells which synthesized alpha 2 M by immunoprecipitation. (4) Serum alpha 2 M levels of normal, immunized animals will be quantitated by rocket immunoelectrophoresis and/or radioimmunoassays. Once the biological characteristics are determined for normal animals and normal cells, the investigation will be extended to study the same qualities in tumor bearing animals and in-vitro transformed cell lines. The results obtained from the proposed research will provide information on how protease/protease inhibitor systems may aid regulation of cellular proliferation and/or differentiation and more specifically how the interaction of tumor cells and the immune system may result in immunosuppression through these molecules.